RESUMO
BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15âyears conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000âcopies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59âyears (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15âyears, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24âyears and in certain provinces. Among persons aged 15-59âyears, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.
Assuntos
Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , HIV , Zâmbia/epidemiologia , Carga Viral , Prevalência , Incidência , Estudos TransversaisRESUMO
To cluster anal microbiota and define microbial patterns associated with biological, clinical, and behavioral correlates among Nigerian men who have sex with men (MSM) living with or at risk for HIV. In this cross-sectional pilot study, the 15 most abundant 16S taxa in the anal microbiota of 113 MSM underwent unsupervised K-means clustering and z-score comparisons to define similarities and dissimilarities among 4 microbiota taxonomic profiles. Distributions of oncogenic HPV (high-risk human papillomavirus [HR-HPV]), concurrent HIV, antiretroviral therapy (ART), and other clinical and behavioral data were evaluated using Fisher's exact and Kruskal-Wallis tests to determine biological signatures of cluster membership. Prevotella was consistently represented in each cluster, but the average composition ranged from 14% to 44%. Cluster 2 was enriched with a member of the Fusobacteria phylum, Sneathia (29%). More participants of cluster 2 were HIV infected and taking ART (83%, 5/6), were virally suppressed (80%, 4/5), had HPV-16 (66.7%, 4/6), and reported no vaginal sex partners (83%, 5/6). HPV-35, a highly prevalent oncogenic HPV in Nigeria, was observed in all clusters except cluster 2 (0%, 0/6). Other covariates were similar across clusters (all p > .05). K-means unsupervised clustering, a canonical pattern recognition method, generalized the microbial community composition and structure while accounting for among sample variability. Further studies are needed to evaluate whether an anal microbial community enriched with members of the Fusobacteria phylum is associated with HIV-infected MSM who are virally suppressed and have a concurrent HPV-16.
Assuntos
Canal Anal/microbiologia , Microbioma Gastrointestinal , Soropositividade para HIV/microbiologia , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/microbiologia , Minorias Sexuais e de Gênero , Adolescente , Adulto , Antirretrovirais/uso terapêutico , Estudos de Coortes , Coinfecção , Estudos Transversais , HIV/imunologia , Soropositividade para HIV/tratamento farmacológico , Homossexualidade Masculina , Humanos , Masculino , Nigéria/epidemiologia , Projetos Piloto , Prevalência , Comportamento Sexual , Adulto JovemRESUMO
We isolated a strain of human mycoplasma that promotes lymphomagenesis in SCID mice, pointing to a p53-dependent mechanism similar to lymphomagenesis in uninfected p53-/- SCID mice. Additionally, mycoplasma infection in vitro reduces p53 activity. Immunoprecipitation of p53 in mycoplasma-infected cells identified several mycoplasma proteins, including DnaK, a member of the Hsp70 chaperon family. We focused on DnaK because of its ability to interact with proteins. We demonstrate that mycoplasma DnaK interacts with and reduces the activities of human proteins involved in critical cellular pathways, including DNA-PK and PARP1, which are required for efficient DNA repair, and binds to USP10 (a key p53 regulator), impairing p53-dependent anticancer functions. This also reduced the efficacy of anticancer drugs that depend on p53 to exert their effect. mycoplasma was detected early in the infected mice, but only low copy numbers of mycoplasma DnaK DNA sequences were found in some primary and secondary tumors, pointing toward a hit-and-run/hide mechanism of transformation. Uninfected bystander cells took up exogenous DnaK, suggesting a possible paracrine function in promoting malignant transformation, over and above cells infected with the mycoplasma. Phylogenetic amino acid analysis shows that other bacteria associated with human cancers have similar DnaKs, consistent with a common mechanism of cellular transformation mediated through disruption of DNA-repair mechanisms, as well as p53 dysregulation, that also results in cancer-drug resistance. This suggests that the oncogenic properties of certain bacteria are DnaK-mediated.